Complementary chromosome folding by transcription factors and cohesin

Abstract

The spatial organisation of interphase chromosomes is known to affect genomic function, yet the principles behind such organisation remain elusive. Here, we first compare and then combine two well-known biophysical models, the transcription factor (TF) and loop extrusion (LE) models, and dissect their respective roles in organising the genome. Our results suggest that extrusion and transcription factors play complementary roles in folding the genome: the former are necessary to compact gene deserts or \"inert chromatin\" regions, the latter are sufficient to explain most of the structure found in transcriptionally active or repressed domains. Finally, we find that to reproduce interaction patterns found in HiC experiments we do not need to postulate an explicit motor activity of cohesin (or other extruding factors): a model where co-hesin molecules behave as molecular slip-links sliding diffusively along chromatin works equally well.